NMP22 Levels Research Articles

Association of FGFR alterations with FGFR 1-4 gene expression in TUR biopsies and matched NMP22 urine levels in early bladder cancer of the prospective real world clinico-pathological register trial: BRIDGister.

e16533 Background: The objective of the present study was to identify molecular charactersitics associated with FGFR positive tumors in matched urine and TUR biopsy samples from patients being suspicious of bladder cancer and undergoing first TURB at the pilot center of the multicentric BRIDGister Real World Experience trial that are helpful for patient management and prognosis. Methods: For this pilot study paraffin fixed pretreatment tissue samples from the first TURB of 28 pts participating in the BRIDGister trial and matched urine samples were prospectively collected and analyzed. RNA from FFPE tissues were extracted by commercial kits and analyzed by Therascreen FGFR IVD kit (Qiagen GmbH, Hilden). Relative gene expression of subtyping markers (KRT5, KRT0) as well as FGFR1, FGFR2, FGFR3, FGFR4, ERBB2 was centrally tested by standardized test systems (STRATIFYER Molecular Pathology GmbH, Cologne). In addition urine samples were analyzed by commercially available urine tests (UBC Rapid, BTA stat, NMP22). Spearman correlation, Kruskal-Wallis, MannWhitney and Sensitivity/Specificity tests were done by JMP 9.0.0 (SAS software). Results: The pilot cohort of the BRIDGister trial consisted of 28 patients (median age: 73, male 71% vs female 29%) of diverse clinical stages (Benign lesions/no tumor 21%, pTa 32%, pT1 21%, pT2 21%) and WHO 1973 grade (G1 7%, G2 43%, G3 21%). Based on FFPE tissue testing using Therascreen FGFR IVD kit 9 out of 28 patients exhibited FGFR alterations (32%). FGFR positive tumors were associated with high expression of FGFR3 mRNA (r = 5.951, p = 0.0011) but low FGFR1 mRNA as well as FGFR4 mRNA (r = -0.3882, p = 0.0412 and r = -0.6305, p = 0.0004, respectively). Interestingly, FGFR alteration was positively associated with the basal marker KRT5 (r = 0.3929, p = 0.0386), but not with luminal KRT20 mRNA expression (r = -0.0208, p = 0.9179). Moreover FGFR3 altered bladder cancer was associated with elevated NMP22 levels in pretreatment urine (r = 0.3978, p = 0.0361). Conclusions: In early bladder cancer FGFR3 alterations are tightly associated with a characteristic FGFR mRNA signature. Mutation/Fusion of FGFR3 results in high FGFR3 but low FGFR1 and FGFR4 mRNA expression, which might be i.a. relevant for the response to FGFR inhibition and important to predict outcome of FGFR inhibitors. Morever FGFR alteration was associated with elevated NMP22 urine levels, which might be helpful for detecting and monitoring FGFR altered bladder cancer in a non invasive fashion. These results warrant further investigation and its impact on outcome prediction (BCG responsiveness, recurrence, proegression, etc) will be prospectively analyzed in the framework of the ongoing multicenter BRIDGister Real World Experience trial.

Evaluation of NMP22 in bladder cancer patients sensitive to environmental toxins.

Bladder cancer (BC) is recognized as environmentally related. The interaction of environmental exposure to chemicals and genetic susceptibility seem to play important roles in BC development. In order to improve diagnosis and the recognition of BC risk, a group of markers which combine genetic susceptibility with detoxification and nuclear matrix protein (NMP22) is proposed. The aim of the study was to examine the utility of nuclear matrix protein (NMP22) as a diagnostic marker in BC in genetic susceptibility (NAT2 slow acetylators) combined with detoxification abilities (glutathione S-transferase GST and isoenzyme GST-π). The NMP22 level in urine, N-acetyltransferase 2 (NAT2) genotype and GST activity in hemolysate blood, as well as isoenzyme GST-π level, were determined in the urine and serum of 43 patients with BC and from 25 non-cancer controls. NMP22 and isoenzyme GST-π levels were measured by ELISA. The NAT2 genotype was examined in DNA isolated from whole blood using the PCR (Polymerase Chain Reaction) technique, while the activity of GST was determined with the spectrophotometric method. In the BC group, NMP22 (p = 0.005) concentration, GST-π (p = 0.003) in urine and GST (p = 0.009) activity in blood were statistically significantly higher than in the healthy controls. The majority of BC patients were slow acetylators (NAT2 genotype). A correlation between the level of nuclear matrix protein NMP22 and GST was found in all BC group (p = 0.007) and also slow acetylators (p = 0.0147). The results support the utility of a marker combination, which covers the genetic susceptibility to chemicals with the level of detoxification and nuclear matrix protein in BC patients. A relationship between NMP22 level in urine, GST level in blood and NAT2 genotype was observed. Also the isoenzyme GST-π in urine seems useful as a marker of BC.

Urinary Tumor Markers Could Predict Survival in Bladder Carcinoma

The early diagnosis of bladder cancer is important for effective treatment of the disease. This study aimed to evaluate the nuclear matrix protein 22 (NMP 22), soluble epithelial cadherin (E-cadherin), cathepthin-D and total protein with clinico-pathological features of bladder cancer, and to determine the relation between each marker and tumor progression after treatment. The study includes 65 patients with bladder cancer, 14 benign urinary diseases and 11 healthy volunteers. Patients were categorized according to bilharzial infestation, T stage, tumor grade, size and the presence of lymph node metastasis. Forty patients were followed for disease progression after surgery. There was a significant increase of NMP22, E-cadherin, cathepthin-D and total protein detected in cancer group compared to healthy and benign groups. It was found that NMP 22 and E-cadherin had highest sensitivity (84.4, 76.9%, respectively) while, total ddedprotein showed highest specificity (77.4%). Tumor size correlated with urinary NMP22 (r=0.3, p=0.02), although, E-cadherin, cathepsin-D and total protein correlated with tumor size (r=0.3, 0.28, 0.2; p=0.01, p=0.01, 0.04, respectively) and lymph node metastasis (r=0.32, 0.34, 0.2; p=0.003, 0.005, 0.04, respectively). Elevated pretreatment urinary NMP22, E-cadherin and total protein levels was associated significantly with bladder cancer recurrence (p=0.02, 0.001, 0.005, respectively). In conclusion, determination of urinary NMP22, E-cadherin and total protein in bladder cancer patients or persons at risk of developing bladder cancer will help in early detection of the disease and prediction of recurrence. The use of a combination of tumor markers is markedly useful than the assessment of single one.

391 CLINICAL UTILITY OF NMP22 FOR BLADDER CANCER SURVEILLANCE A MULTI-CENTER CROSS-SECTIONAL STUDY

You have accessJournal of UrologyUrothelial Cancer: Natural History & Pathophysiology/Marker1 Apr 2012391 CLINICAL UTILITY OF NMP22 FOR BLADDER CANCER SURVEILLANCE A MULTI-CENTER CROSS-SECTIONAL STUDY Eugene K. Cha, Christopher E. Barbieri, Michael Rink, Thomas F. Chromecki, Allison Dunning, Yair Lotan, Harun Fajkovic, Douglas S. Scherr, Madhu Mazumdar, and Shahrokh F. Shariat Eugene K. ChaEugene K. Cha New York, NY More articles by this author , Christopher E. BarbieriChristopher E. Barbieri New York, NY More articles by this author , Michael RinkMichael Rink New York, NY More articles by this author , Thomas F. ChromeckiThomas F. Chromecki Graz, Austria More articles by this author , Allison DunningAllison Dunning New York, NY More articles by this author , Yair LotanYair Lotan Dallas, TX More articles by this author , Harun FajkovicHarun Fajkovic St. Poelten, Austria More articles by this author , Douglas S. ScherrDouglas S. Scherr New York, NY More articles by this author , Madhu MazumdarMadhu Mazumdar New York, NY More articles by this author , and Shahrokh F. ShariatShahrokh F. Shariat New York, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.455AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The urinary biomarker NMP22 has been FDA-approved for the surveillance of patients with bladder cancer. However, the use of NMP22 has not been widely incorporated into clinical practice. We sought to employ decision curve analysis to determine the impact of NMP22 on clinical decision-making for the surveillance of bladder cancer patients using data from a prospective trial. METHODS The study included 668 patients with a history of non-muscle-invasive bladder cancer who underwent cystoscopy, urine cytology, and measurement of urinary NMP22 levels. We constructed several prediction models to estimate risk of bladder cancer. The base model was generated using patient characteristics (age, gender, race, and history of intravesical therapy); cytology and NMP22 were added to the base model to determine effects on predictive accuracy. Clinical net benefit was calculated by summing the benefits and subtracting the harms and weighting these by the threshold probability at which a patient or clinician would opt for cystoscopy. RESULTS Ninety-seven patients were found to have recurrence of bladder cancer (14.5%). In univariable analyses, NMP22 was the strongest predictor of bladder cancer presence (predictive accuracy 66.0%), followed by cytology (56.5%) and history of intravesical therapy (56.4%). In multivariable prediction models, NMP22 improved the predictive accuracy of the base model by 11.5% (AUC 59.2% to 70.7%, p<0.0001) and that of the base model plus cytology by 6.4% (AUC 64.3% to 70.7%, p=0.036). Decision curve analysis revealed that adding NMP22 to other models increased clinical benefit, particularly at higher threshold probabilities. CONCLUSIONS NMP22 is a strong, independent predictor of bladder cancer in patients undergoing surveillance. Addition of NMP22 improves the accuracy of standard predictors by a statistically and clinically significant margin. Decision curve analysis suggests that integration of NMP22 into clinical decision-making helps spare unnecessary cystoscopies, with minimal increased risk of missing a bladder cancer recurrence. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e160 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eugene K. Cha New York, NY More articles by this author Christopher E. Barbieri New York, NY More articles by this author Michael Rink New York, NY More articles by this author Thomas F. Chromecki Graz, Austria More articles by this author Allison Dunning New York, NY More articles by this author Yair Lotan Dallas, TX More articles by this author Harun Fajkovic St. Poelten, Austria More articles by this author Douglas S. Scherr New York, NY More articles by this author Madhu Mazumdar New York, NY More articles by this author Shahrokh F. Shariat New York, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract 3767: Detection biomarkers for squamous cell bladder carcinoma in a global setting

Abstract Bladder cancer is the fifth common malignancy in the US, and internationally it is the second most common cause of mortality from genitourinary malignancies after prostate cancer. Current clinical practice and recommendations do not include early screening for prevention. The use of cystoscopy cannot become a routine screening method of early detection due to limitations, including cost, while cytology is specific but not sensitive. Biomarkers that screen for bladder cancer before it becomes invasive are an alternative viable solution if validated and made cost-effective. Studies have mostly looked at translational cell bladder cancer and not squamous cell bladder cancer that is much more common in many parts of Africa, including Egypt and related to Schistomiasis parasitic infection. The aim in this study was to validate the use of three FDA approved biomarkers of early detection of translational baldder cancer on squamous bladder cancer in Egypt. The NMP22, Telomerase, and CD44 test kits were used for urine sample from 60 squamous bladder cancer patients and 60 non-cancer population controls. The cases and the controls were recruited from the Urology and Nephrology Center at Mansora University in Mansora, Egypt. Patients were diagnosed by cytoscopy and cytology. There was a significant difference in mean NMP22, CD44 and Telomerase levels among cases compared to controls. However, when adjusting for age and sex, only NMP22 and Telomerase remained significant. There was no significant difference among bladder cancer patients for presence or absence of a mass or schistomiases infection. CD44 and NMP22 mean levels were higher among patients if they were with stages 3 or 4 of bladder cancer compared to stages 1or 2 but this did not reach statistical significance. NMP22 and Telomerase biomarkers had better specificity and sensitivity than CD44 in predicting bladder cancer as shown by the Receiver Operating Characteristics (ROC) curves. In Conclusion, these biomarkers are satisfactory for detection of squamous cell bladder cancer, especially NMP22 and telomerase, and can become routinely used in the clinical setting in developing countries with high percentage of squamous cell bladder cancer. The next phase of biomarker validation for these assays among high-risk populations is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3767.

1175 LONG TERM OUTCOME OF PATIENTS FOLLOWED FOR NON-MUSCLE INVASIVE BLADDER CANCER (NMI-BC) PRESENTING WITH POSITIVE NMP22 AND NEGATIVE CYTOLOGY AND CYSTOSCOPY

You have accessJournal of UrologyBladder Cancer: Detection and Screening1 Apr 20101175 LONG TERM OUTCOME OF PATIENTS FOLLOWED FOR NON-MUSCLE INVASIVE BLADDER CANCER (NMI-BC) PRESENTING WITH POSITIVE NMP22 AND NEGATIVE CYTOLOGY AND CYSTOSCOPY Vincenzo Serretta, Fabio Scuto, Antonina Ruggirello, Dario Passalacqua, Rosalinda Allegro, and Darvinio Melloni Vincenzo SerrettaVincenzo Serretta More articles by this author , Fabio ScutoFabio Scuto More articles by this author , Antonina RuggirelloAntonina Ruggirello More articles by this author , Dario PassalacquaDario Passalacqua More articles by this author , Rosalinda AllegroRosalinda Allegro More articles by this author , and Darvinio MelloniDarvinio Melloni More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.675AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES NMP22 has been introduced in diagnosis and follow-up of bladder cancer. Although several causes of false positive results have been identified, the clinical value of positive NMP22 is often doubtful. We present the long term outcome of patients in follow-up for previous NMI bladder cancer presenting with NMP elevated values in spite of negative cytology, cystoscopy and urography. METHODS A urine collection kit, containing urine stabilizer and a test kit using MAb302-18 and MAb302-22, developed by Matritech Inc. was used. Urine samples were obtained in all patients after a single spontaneous void and frozen at -20°C immediately after collection. A cut-off value of 10 units/ml was adopted. A positive NMP22 was obtained in 95 patients in follow-up for Ta-T1 G1-3 bladder cancer. In 50 patients (53%) intravesical chemotherapy was given and urine was obtained after an interval of 7-30 days. Cytology, cystoscopy and urography were negative. No other urological pathology was evident except for asymptomatic BPH. Since 1996 all patients were maintained into a close follow-up with urinary cytology and cystoscopy every 3 months for the first 2 years and 6-monthly thereafter. All suspicious lesions at cystoscopy were biopsied. A bladder mapping was performed in the case of negative cystoscopy and positive or doubt cytology. RESULTS Median follow-up was 51 months (range: 2-174). Five patients only (5%) were lost at follow-up before 2 years and 3 patients died. The median interval between the last recurrence and NMP22 determination was 39 months. Thirty-seven (39%) patients recurred at a mean interval of 13 months from NMP22 test. No significant difference was evident in NMP22 levels between recurring and recurrence-free patients (p=0.26). The results were not influenced by intravesical chemotherapy (p=0.87). No clinically relevant difference emerged in recurrence-free survival according to NMP22 values higher or lower than 10 U/ml (38 vs 31 months) although statistically significant. CONCLUSIONS Positive urine NMP22 in patients in follow-up for previous NMI-BC is not associated with a higher risk of recurrence when accompanied by negative cytology and cystoscopy. Palermo, Italy© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e455 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Vincenzo Serretta More articles by this author Fabio Scuto More articles by this author Antonina Ruggirello More articles by this author Dario Passalacqua More articles by this author Rosalinda Allegro More articles by this author Darvinio Melloni More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Expression and clinical significance of nuclear matrix protein 22 and cytokeratin 18 in transitional cell carcinoma of the bladder

To evaluate the expression and clinical significance of urinary nuclear matrix protein (NMP22) and cytokeratin 18 (CK18) for transitional cell carcinoma of the bladder. Urinary NMP22 and CK18 levels of 293 patients with transitional cell carcinoma of the bladder, 400 patients with non-transitional cell carcinoma of the bladder, and 105 bladder benign disease were analysed by enzyme-linked-immunosorbent assay (ELISA). The levels of urinary NMP22 and CK18 in the patients with transitional cell carcinoma of the bladder (M = 17.3 U/ml, M(CK18) = 484.2 U/L) were significantly higher than those in the non-transitional cell carcinoma of the bladder (M = 6.8 U/ml, M(CK18) = 156.0 U/L) and the benign disease group (M(NMP22) = 2.3 U/ml, M(CK18) = 66.6 U/L) (P < 0.001). The sensitivity and specificity of urinary NMP22 and CK18 were 79.2%, 88.6% and 78.2%, 82.9%, respectively, for transitional cell carcinoma of the bladder before any treatment. The joint sensitivity of the two markers was 91.7%. The NMP22 and CK18 levels were significantly lower in the recovered patients after surgical operation (P < 0.01), while in patients with recurrence or metastasis the levels of the markers were significantly higher (P < 0.01). There was a significant relationship between NMP22 and CK18, (r = 0.689, P < 0.01). The levels of urinary nmp22 and CK18 were significantly different among pathological grade G1, G2, G3, and stage Ta, T1, T2, T3 (P < 0.01). NMP22 and CK18 are useful tumor marker for diagnosis of transitional cell carcinoma of the bladder and for monitoring the state of illness. The joint use of the two markers can improve the sensitivity of cancer detection. NMP22 and CK18 may become a new class of tumor markers, and to be the basis for development of a new assay with an increased efficacy for the detection and treatment of bladder cancer.

Urinary insulin‐like growth factor 2 identifies the presence of urothelial carcinoma of the bladder

To examine urinary insulin-like growth factor 2 (IGF-2) levels in patient urine samples and determine the potential of IGF-2 as a marker for the presence of urothelial carcinoma of the bladder (UCB). The current gold standard for diagnosis of UCB is cystoscopy and cytological analysis. The identification of an accurate urine marker for UCB with the potential to replace unnecessary cystoscopy would benefit patients with UCB and others investigated after detecting haematuria. In the present study, we analysed 65 urine samples, and optimized an enzyme-linked immunosorbent assay-based approach to measure urinary levels of IGF-2. Based on a threshold of 5.4 ng/mL, patients with UCB have significantly elevated levels of urinary IGF-2 (P = 0.009) and this difference remained significant after adjustment for age and sex (P = 0.04). Sensitivity and specificity values of 80% and 52%, respectively, were determined for urinary IGF-2 alone and when combined with nuclear matrix protein 22 (NMP22; an approved biomarker for detection of UCB). There was a positive correlation between urinary IGF-2 levels and NMP22 levels in patient urine samples and the combined assay improved the detection of UCB (sensitivity 85% and specificity 52%). Substantiated evidence has identified IGF-2 as a valuable marker for UCB. In addition, the novel observations of the present study have shown that aberrant levels of IGF-2 occurring in the presence of UCB, can now be determined through a simple and inexpensive urine assay.

Influencia del retraso en el procesamiento preanalítico de la orina en la determinación del NMP22

ObjectivesTo evaluate the influence of the delay in urinary nmp22 preanalytical processing. Material and methodsTwenty-eight voided urine samples were taken: bladder cancer (14), urine tract infections (4), lithiasis (4), healthy volunteers (1), and with other no malignant bladder diseases (5). All samples, were maintained at environment temperature, and were processed according to the stabilization of parts of urine collected at 0, 30, 90 and 150 minutes. Samples were stored at 4 °C until its determination. nmp22 was determined with the IMMULITE One analyzer. ResultsThere were no significant differences for nmp22 levels between each different point of time studied. ConclusionsDelay up to 2 hours and a half when we add stabilization solution to urine samples no affects nmp22 results. That thing, might provide more confidence and flexibility on quantitative immunoassays that required urine stabilization.

Urinary Survivin Test Compared to the Nuclear Matrix Protein (NMP)-22 Test and Urine Cytology for the Diagnosis of Bladder Cancer

Purpose: The aim of this study was to compare the sensitivity and specificity of the urinary survivin test for the diagnosis of bladder cancer with the nuclear matrix protein (NMP)-22 test and the urine cytology, and we wanted to correlate survivin with the tumor stage and grade. Materials and Methods: Between October 2002 and March 2004, voided urine samples were obtained from 41 patients with bladder cancer and also from 36 controls who had no evidence of bladder cancer. The urinary survivin and NMP-22 levels were measured using a DuoSet IC ELISA kit and an automated chemiluminescent assay system. The results were compared with the cytologic results and the pathologic findings. Results: The comparative results showed the higher sensitivity for the urinary survivin test (78.0%) and the NMP-22 test (75.6%) than for the urine cytology (65.8%) for the detection of bladder cancer. The specificity of urinary survivin (86.1%) and urine cytology (97.2%) were higher than that for the NMP-22 test (66.6%). Measuring the urinary survivin level was a more accurate test than the urinary NMP-22 test and the urine cytology for the detection of lower grade and superficial bladder cancer. Conclusions: The urinary survivin test was superior to urine cytology for sensitivity and specificity, and these two parameters of the urinary survivin test were higher than those of the NMP-22 test. Especially, the urinary survivin test is an accurate diagnostic test for superficial and lower grade bladder tumor. Our results suggested that the urinary survivin test appears to be a reliable diagnostic test to identify patients with bladder cancer. (Korean J Urol 2006;47:1041-1045) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

Evaluation of the Clinical Value of Urinary NMP22 as a Marker in the Screening and Surveillance of Transitional Cell Carcinoma of the Urinary Bladder

Purpose: To prospectively evaluate the clinical role of urinary NMP22 as a marker for transitional cell carcinoma of the urinary bladder in screening and surveillance settings. Patients and Methods: Single voided specimens were obtained from 211 consecutive patients who presented for flexible cystoscopy. Of these, 96 patients presented with haematuria or irritative symptoms (screening), the remaining 115 were patients with known transitional cell carcinoma on follow–up (surveillance). The urine sample was used for urine microscopy, cytology and for measuring NMP22 levels. Results: Bladder tumours were found in 16 of 96 (16.6%) patients in the screening group and 17 of 115 (15.6%) patients on surveillance. The NMP22 levels were significantly lower in patients with lower stage (Ta vs. T1–3), low grade (G1, G2 vs. G3, CIS) and papillary morphology. The optimum threshold for NMP22 obtained from the ROC curve was 4.75 U/ml, providing a sensitivity, specificity, positive predictive value and negative predictive value of 42.4, 85, 38.5 and 88.6%, respectively. Sensitivity and specificity were better in patients being screened than in those on surveillance. In both groups, urinary NMP22 had similar diagnostic characteristics as urinary cytology. Conclusions: Urinary NMP22 levels are significantly higher in patients with bladder tumour than in those negative for tumours, and test predictability improves with increasing stage and grade. The overall sensitivity for urinary NMP22 is similar to, but not superior to urine cytology. Our study suggests that the clinical role of urinary NMP22 as a diagnostic marker can be at best supportive only.

Urinary NMP22TM and Karyometry in the Diagnosis and Follow-Up of Patients with Superficial Bladder Cancer

Objective: To study the value of two outpatient urine tests with regard to the diagnosis and recurrence of bladder tumors. Methods: Fifty patients with a history of superficial bladder cancer were evaluated with urinary NMP22^TM levels (cutoff level 10 U/ml), bladder wash karyometry (low versus intermediate and high risk) and cystoscopy. All patients were followed for 1 year. Results: Diagnostic negative and positive predictive values (NPV and PPV) of the tests were, respectively: NMP22 91.2 and 56.3%, and karyometry 80 and 33.3%. Prognostic NPV and PPV with regard to a subsequent recurrence were, respectively: NMP22 77.8 and 27.3%, and karyometry 82.6 and 50%. Conclusion: The diagnostic value of NMP22 is good. Since the 3 false-negative results were in low-stage and low-grade lesions, this test could be used as a prescreening for cystoscopy. The NPV of these tests with regard to tumor recurrence is around 80%, but only karyometry has a significant PPV. Change in the follow-up policy on the basis of these tests remains difficult. In patients with neobladders NMP22 appears to be of little use, because of the high urinary NMP22 levels in the absence of malignancy.

COMPARISON OF URINE COLLECTION METHODS FOR EVALUATING URINARY NUCLEAR MATRIX PROTEIN, NMP22, AS A TUMOR MARKER

Purpose The nuclear matrix protein, NMP22, has been shown to be a useful tumor marker for identifying patients with a high likelihood of rapid recurrence of transitional cell carcinoma of the urinary tract after surgical treatment. Currently measurement of NMP22 involves 3 urine voids collected during a 24-hour period, which are pooled and assayed as a single sample. This study was performed to determine whether any single void would yield similar results to the pooled 3-void sample. Materials and Methods A total of 2,018 urine samples (3 voids per sample) was included in the study. All analyses were performed using the nonparametric Wilcoxon signed rank test for matched pairs. Results Analysis showed that the NMP22 level of a single void collected between midnight and noon was similar to the NMP22 level of the pooled 3-void sample. Receiver operating characteristics curves of the midnight-to-noon single void and the pooled 3-void sample were similar for predicting recurrence postoperatively in patients with urinary tract transitional cell carcinoma. Conclusions One void collected between midnight and noon compares favorably with the current 3-void collection method for determining NMP22 levels in urine.

Urinary Nuclear Matrix Protein as a Marker for Transitional Cell Carcinoma of the Urinary Tract

Purpose The purpose of this trial was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, * * Matritech, Inc., Newton, Massachusetts. as an indicator for transitional cell carcinoma of the urinary tract. Materials and Methods Three groups of subjects participated in this trial of NMP22: 1--175 with transitional cell carcinoma, 2--117 with benign urinary tract conditions and 3--375 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of study entry. Each sample was assayed for the level of NMP22. Results In normal healthy volunteers and in subjects with benign conditions median NMP22 levels were 2.9 and 3.3 units per ml., respectively. Median urinary NMP22 levels in patients with transitional cell carcinoma were significantly greater than in comparison subjects. Patients with active transitional cell carcinoma had significantly greater median urinary NMP22 levels than those with no evidence of disease (6.04 versus 4.11 units per ml., p = 0.027, 1-tailed Mann-Whitney U test). We noted no effect of tumor grade, extent of disease or exposure to intravesical therapy on urinary NMP22 levels. Conclusions NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.